Rahul N. Khurana

Linezolid-induced optic neuropathy: a mitochondrial disorder?

We report a case of bilateral mitochondrial optic neuropathies secondary to long-term linezolid treatment, show the nature of recovery, review the findings in the literature and propose a potential mitochondrial mechanism for linezolid-induced mitochondrial optic neuropathy. This is an observational case report and literature review with presentation of the clinical course of linezolid mitochondrial optic neuropathies through clinical and psychophysical documentation. Main outcome measures included: visual acuity, funduscopical examinations and peripapillary retinal nerve fibre layer (PRNFL) optical coherence tomography (OCT). A 6-year-old boy presented with bilateral optic neuropathies secondary to 1 year of linezolid treatment for osteomyelitis of the mandible. On presentation, visual acuities were 20/400 in both eyes, with considerable optic disc oedema, hyperaemia and PRNFL swelling confirmed by OCT. 2 weeks after the discontinuation of linezolid, visual acuities returned to 20/25 in both eyes, with reduction in the optic disc oedema, hyperaemia and PRNFL swelling. 3 months after the discontinuation of linezolid treatment, visual acuities were stable at 20/20 in both eyes, with a marked decrease in PRNFL swelling confirmed by OCT, and the development of mild temporal optic disc pallor in both eyes. Doctors should be aware of impairments of vision among patients on long-term linezolid treatment and promptly discontinue treatment to prevent irreversible vision loss. The development and resolution of bilateral optic neuropathies with considerable PRNFL swelling in this patient provide insight into the more general rubric of mitochondrial optic neuropathies.

Optical coherence tomography to assess intrastromal corneal ring segment depth in keratoconic eyes.

PURPOSE: To investigate intrastromal corneal ring segment depth with a high‐speed corneal optical coherence tomography (OCT) system. SETTING: Doheny Eye Institute, University of Southern California, Los Angeles, California, USA. METHODS: A prospective observational case series comprised 4 eyes of 4 patients receiving Intacs intrastromal corneal ring segments (Addition Technology, Inc.) for keratoconus. Optical coherence tomography (OCT) was performed between 7 days and 43 days after implantation. RESULTS: The slitlamp impression of intrastromal corneal ring segment implantation depth did not correlate well with OCT measurements (r2 = 0.68). The fractional implantation depth was correlated with several surgical variables using a stepwise multivariate regression model, and 2 statistically significant correlations were found. The position of the distal portions of the ring segments was shallower than that of the portion closer to the insertion site (P = .003). Segments placed in the inferior cornea (P = .008) experienced more distal shallowing. Shallower depth was associated with greater fractional anterior stromal compression (P = .04). CONCLUSIONS: Shallower placement of intrastromal corneal ring segments may result in more complications, such as epithelial–stromal breakdown and extrusion, because of the greater anterior stromal tensile strain. The distal and inferior portions of intrastromal corneal ring segments tended to be placed at a shallower depth. Optical coherence tomography provided precise measurement of ring segment depth and may help identify implants that pose a greater risk for depth‐related complications.

Mitochondrial Oxidative DNA Damage in Experimental Autoimmune Uveitis

PURPOSE In experimental autoimmune uveitis (EAU), recent work has demonstrated that retinal damage involves oxidative stress early in uveitis, before macrophage cellular infiltration. The purpose of this study was to determine whether oxidative mitochondrial DNA damage occurs early in EAU, before leukocyte infiltration. METHODS Lewis rats were immunized with S-antigen mixed with complete Freund adjuvant (CFA) to induce EAU. Nonimmunized animals and animals injected with CFA served as controls. Animals were killed on days 3, 4, 7, and 12 after immunization. Damage to mitochondrial DNA and nuclear DNA was assessed using a novel long quantitative polymerase chain reaction technique. TUNEL staining to detect apoptosis and immunohistochemical detection of leukocyte infiltration in EAU retinas were also performed at these times. RESULTS Mitochondrial DNA damage occurred early in EAU, from day 4 to day 12. In the early phase of EAU (days 4-7), there was no inflammatory cell infiltration. On day 12 inflammatory cells infiltrated the retina and uvea. Nuclear DNA damage occurred later in EAU at day 12. Neither mitochondrial nor nuclear DNA damage was detected in the controls. TUNEL-positive staining for apoptosis was detected only at day 12 in EAU retina. CONCLUSIONS Oxidative mitochondrial DNA damage begins at day 4 in EAU, supporting the view that oxidative stress selectively occurs in the mitochondria in the early phase of EAU, before leukocyte infiltration. Such oxidative damage in the mitochondria may be the initial event leading to retinal degeneration in EAU.

Influence of Glycosylated Hemoglobin on the Efficacy of Ranibizumab for Diabetic Macular Edema: A Post Hoc Analysis of the RIDE/RISE Trials

PURPOSE To investigate the influence of glycosylated hemoglobin (HbA1c) on treatment outcomes in patients with diabetic macular edema (DME) receiving intravitreal ranibizumab. DESIGN Post hoc analysis of 2 identical phase III clinical trials assessing the efficacy and safety of intravitreal ranibizumab in DME over 36 months (RIDE: NCT00473382/RISE: NCT00473330). PARTICIPANTS A total of 483 adults with vision loss from DME treated with ranibizumab were included in this analysis from RIDE/RISE. Participants received monthly intravitreal ranibizumab (0.3 or 0.5 mg). MAIN OUTCOME MEASURES Differences in visual and anatomic outcomes, and diabetic retinopathy (DR) severity score, between subgroups of patients with baseline HbA1c ≤7% versus HbA1c >7% at 36 months. RESULTS There were 195 patients in RIDE/RISE who were treated with ranibizumab with a baseline HbA1c ≤7% and 288 patients with a baseline HbA1c >7% included in this analysis. The mean improvement in visual acuity (VA) at 36 months was +13 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in patients with baseline HbA1c ≤7% compared with +11 ETDRS letters in the patients with a baseline HbA1c >7% (P = 0.17). After adjustment for baseline central foveal thickness (CFT) and duration of diabetes, the mean CFT reduction was -268 μm in patients with a baseline HbA1c ≤7% and -269 μm in patients with a baseline HbA1c >7% (P = 0.98; 95% confidence interval, -22.93 to 23.54). The proportion of patients with a ≥2-step improvement in DR severity score was 38% in patients with baseline HbA1c ≤7% compared with 41% in the patients with a baseline HbA1c >7% (P = 0.53). There was no correlation of baseline HbA1c with any visual or anatomic parameter. CONCLUSIONS The improvement in VA, anatomic reduction of macular edema, and improvement in DR severity score with ranibizumab treatment seem to be independent of baseline HbA1c.

EFFICACY AND SAFETY OF DEXAMETHASONE INTRAVITREAL IMPLANT FOR PERSISTENT UVEITIC CYSTOID MACULAR EDEMA.

Purpose: To investigate dexamethasone intravitreal implant (DEX Implant 0.7 mg, Ozurdex; Allergan, Inc, Irvine, CA) as a treatment for persistent cystoid macular edema (CME) secondary to uveitis. Methods: Treatment and outcomes data were collected retrospectively for 18 eyes from 13 consecutive patients treated with the DEX Implant for persistent, noninfectious uveitic CME. Outcome measures included the cumulative incidence of resolution of CME, visual acuity, central retinal thickness (measured by spectral domain optical coherence tomography), and vitreous haze score. Results: After a single DEX Implant, there was no detectable CME in 89% and 72% of eyes at 1 month and 3 months, respectively. The median time to recurrence of CME (±standard error) was 201 ± 62 days. The percentage of eyes with no recurrence of CME was 35% at 6 months and 30% at 12 months. At 3 months, there was a significant improvement from baseline in mean visual acuity (+2.1 lines, P < 0.01). Eyes with an epiretinal membrane at baseline had shorter time to recurrence of CME and smaller improvements in visual acuity and central retinal thickness than eyes without an epiretinal membrane. At least 1 episode of intraocular pressure >25 mmHg occurred within the first 3 months in 11% (2 of 18) of eyes; all effectively managed with topical hypotensive medications. Conclusion: A single DEX Implant produced sustained improvements in both visual acuity and retinal thickness in the majority of eyes with persistent uveitic CME. Uveitic CME did gradually recur in most eyes; however, close posttreatment monitoring is recommended.

Central retinal vein occlusion in Wegener’s granulomatosis without retinal vasculitis

The classic type of Wegener’s granulomatosis is characterised by necrotising granulomatous lesions of the upper and lower respiratory tracts, generalised focal necrotising vasculitis and glomerulonephritis, whereas the limited type has no renal involvement.1 Ocular manifestations occur in 30–50% of the patients,1 with retinal involvement less frequent and varying from 1 to 13% in the literature.2,3 We report a case of Wegener’s granulomatosis presenting with a central retinal vein occlusion (RVO) without clinical evidence of intraocular inflammation or retinal vasculitis. A 22-year-old white man presented with a 1-week history of intermittent obscuration of vision in his right eye. His medical history was remarkable for classic Wegener’s granulomatosis that had been in remission for the past year. His best-corrected visual acuities were 20/25 in the right eye and 20/20 in …

Anti-VEGF therapeutic approaches for diabetic macular edema.

Diabetic retinopathy is the leading cause of blindness in people of working age. Diabetic macular edema (DME) is the most common cause of moderate vision loss among this population. The Early Treatment Diabetic Retinopathy Study confirmed that argon laser photocoagulation prevents further visual loss but does not improve visual acuity. As a result, many other treatment modalities are being evaluated in the management of DME. Inhibition of vascular endothelial growth factor (VEGF) has become a topic of interest over the past few years in the area of age-related macular degeneration (AMD). The development of ocular anti-VEGF therapy represented a great breakthrough in ophthalmology offering many more therapeutic options. The properties of VEGF and pathophysiology of diabetic retinopathy suggest a role of VEGF antagonists in the management of DME.

Ophthalmic Manifestations of Immune Reconstitution Inflammatory Syndrome Associated with Cryptococcus neoformans

Purpose: To describe the ophthalmic manifestations of immune reconstitution inflammatory syndrome (IRIS) associated with Cryptococcus neoformans. Methods: Four HIV-positive patients on highly active anti-retroviral therapy (HAART) presented with marked optic disk swelling. Results: Three months after the episode of IRIS, 2 of the patients maintained 20/20 visual acuity whose elevated intracranial pressure (ICP) was successfully managed, while 2 patients visual acuities were worse than 20/400 whose ICP was persistently elevated. Conclusion: Cryptococcus is another opportunistic infectious organism associated with IRIS with ophthalmic manifestations. Ophthalmologists have the opportunity to play a key role in the early diagnosis and management to prevent serious visual loss.

Optical coherence tomography findings in paraneoplastic pseudovitelliform lesions in melanoma-associated retinopathy

Purpose To report an unusual case of paraneoplastic pseudovitelliform lesions associated with melanoma-associated retinopathy (MAR). Design Observational case report. Methods Retrospective review of the ophthalmic examination, fundus photography, fluorescein angiography, electroretinogram (ERG), and optical coherence tomography (OCT) of a patient with MAR. Results A 65-year-old Caucasian man with a two-year history of metastatic melanoma was referred for evaluation of a six-month history of nyctalopia. Funduscopic examination in both eyes revealed multiple, creamy, yellow, pseudovitelliform lesions in the posterior pole, varying in size from 100–500 μm, at the level of the outer retinal/retinal pigment epithelium (RPE) junction, coalescing along the inferior portion, with overlying macular neurosensory detachments. OCT showed bilateral macular neurosensory detachments with multiple small areas of high reflectivity at the level of the outer retinal/RPE junction. ERG demonstrated a selective loss of the b-wave and a normal a-wave under dark adapted, scotopic conditions. Conclusion Clinicians should be aware of this atypical presentation of MAR that may include pseudovitelliform retinal findings.

Vogt–Koyanagi–Harada disease presenting as optic neuritis

Vogt–Koyanagi–Harada (VKH) disease is a granulomatous multisystem inflammatory disorder that classically affects the uvea, inner ear, meninges, and skin. We report three patients who presented with initial findings suggestive of bilateral optic neuritis requiring CSF analysis and brain images. None of these patients had extraocular changes. Fluorescein angiography of the retina led to the diagnosis of VKH disease in all patients. Vogt–Koyanagi–Harada disease should be included in differential diagnosis of bilateral optic neuritis, even when extraocular manifestations of the disease are absent. In such cases, fluorescein angiography will aid diagnosis.